CagriSema Outperforms Semaglutide Alone Across Phase 3 REIMAGINE Trials

Cagrilintide/semaglutide (CagriSema), a fixed-dose combination of a long-acting amylin receptor agonist and a glucagon-like peptide-1 receptor agonist (GLP-1 RA), demonstrated superior HbA1c reduction and weight loss compared with semaglutide alone across a trio of phase 3 trials, according to data from the REIMAGINE program presented at the 2026 Scientific Sessions of the American Diabetes Association (ADA) in New Orleans.

CagriSema is being developed by Novo Nordisk as a once-weekly subcutaneous injection combining cagrilintide, a long-acting amylin analogue, with semaglutide. The company submitted CagriSema to the US Food and Drug Administration for weight management in December 2025, based on data from the REDEFINE 1 and REDEFINE 2 trials.

The REIMAGINE program provides the first detailed phase 3 evidence for its use specifically in type 2 diabetes management across early, established, and insulin-treated disease.

REIMAGINE 1

REIMAGINE 1 is a phase 3, randomized, double-blind study evaluating the safety and efficacy of CagriSema in adults with type 2 diabetes who have not responded to diet or exercise, compared to a placebo. The treatment was given as a once-weekly injection for 9 months, followed by a period without treatment to see what happened after stopping the medication.

Among the 189 patients enrolled across the world, results showed that a fixed-dose combination of cagrilintide and semaglutide may help people living with type 2 diabetes lower blood glucose and lose weight early in the disease, and it has the potential to put diabetes into remission with a once-weekly treatment.

REIMAGINE 2

REIMAGINE 2 is a 68-week study comparing CagriSema versus its individual components, cagrilintide and a pair of semaglutide doses, and placebo in 2728 patients with type 2 diabetes whose blood glucose was not well controlled with metformin, with or without a sodium-glucose cotransporter 2 (SGLT2) inhibitor, which are among the most commonly prescribed diabetes medications. Participants were also living with overweight or obesity.

Study results showed a fixed-dose combination of cagrilintide and semaglutide lowered blood glucose more effectively than semaglutide alone, and patients taking CagriSema lost more weight than those on existing therapies.

Of note, analyses and additional assessments of these data are ongoing to further define the effect of CagriSema compared with its individual monocomponents.

REIMAGINE 3

REIMAGINE 3 evaluated the use of CagriSema in 274 adults with type 2 diabetes who were inadequately controlled on basal insulin with or without metformin. Results showed that even in people with long-standing type 2 diabetes already treated with basal insulin, adding a fixed-dose combination of cagrilintide and semaglutide delivered robust improvements in blood glucose with an HbA1c reduction from 8.8% to 6.5%, and weight reductions of up to 12%.

Safety profile and Regulatory Pathway for CagriSema in Type 2 Diabetes

The safety and tolerability profile of CagriSema across the REIMAGINE trials was described as consistent with incretin and amylin-based therapies.¹ In REIMAGINE 3, no severe hypoglycemia occurred despite the addition of CagriSema to ongoing basal insulin therapy — a finding with direct relevance to clinicians managing patients at risk for hypoglycemia in whom intensification is otherwise limited.

"These findings support a potential new therapeutic tool to effectively improve HbA1c levels well below 7% in such a challenging population of inadequately controlled basal insulin-treated type 2 diabetes with the benefit of substantial weight loss, no increase of hypoglycemia risk, and without having to increase insulin doses," said Julio Rosenstock, MD, lead author of the REIMAGINE 3 study.¹ "As we look to provide more solid options for people with type 2 diabetes beyond insulin-based therapies, it's also important to note the safety and tolerability profile was consistent with previous GLP-1 RA trials."

"Rather than focusing on glucose control alone, this strategy addresses weight, cardiovascular risk, and metabolic health together, with the goal of preventing long-term complications and, for some people, fundamentally resetting the trajectory of diabetes itself," said Vanita Aroda, MD, lead author of REIMAGINE 1.¹

References

1. American Diabetes Association. Once-weekly CagriSema (amylin-semaglutide) combination injection more effective than standalone medications. Published June 7, 2026. Accessed June 7, 2026. https://www.prnewswire.com/news-releases/once-weekly-cagrisema-amylin-semaglutide-combination-injection-more-effective-than-standalone-medications-302793308.html

2. Presenters to provide first look at data from REIMAGINE trials of cagrilintide/semaglutide for type 2 diabetes management. ADA Meeting News. Published April 27, 2026. Accessed June 7, 2026. https://www.adameetingnews.org/presenters-to-provide-first-look-at-data-from-reimagine-trials-of-cagrilintide-semaglutide-for-type-2-diabetes-management/